Thermoregulation is a complex function which helps the body maintain a constant temperature by intercommunicating between the core body temperature (CBT), the central nervous system (CNS) and the peripheral vasculature. Dysfunctions of this system resulting in hypo- or hyperthermia may be caused by exogenous heat exposure or endogenous heat production. Endogenous heat production that causes vasomotor symptoms (VMS) such as hot flashes and night sweats has affected 60-80% of all women undergoing natural, chemical or surgical induced menopause. Although hot flashes are the most common symptom affecting many menopausal women, its physiology is still poorly understood today. Studies have attempted to correlate hot flashes to hormonal levels of estradiol, follicle-stimulating hormone and luteinizing hormone, but no relationship has been found. Nevertheless, the use of hormones such as estrogen, progestogens or androgens is known to be an effective way of reducing hot flashes. However, adverse effects such as increased risk of coronary heart disease, thromboembolism, stroke, dementia, and/or breast cancer caused by these hormones have led to a need for alternative therapies.
The use of antidepressants for the treatment of hot flashes has increased over the years. Although the physiology of hot flashes is poorly understood today, there is supportive evidence for the role of norepinephrine (NE) and serotonin (5-HT) in thermoregulation. In particular, studies have revealed an association of increased levels of norepinephrine in the preoptic hypothalamus in the brain to hot flashes. Although studies have shown effective use of various serotonin and norepinephrine reuptake inhibitors such as Paroxetine, Fluoxetine, Venlafaxine, Desvenlafaxine in the treatment of hot flashes, the down side is that patients frequently experience side effects such as dry mouth, decreased appetite, nausea, constipation and sleeplessness, particularly at high dosages. Given the complex functions of thermoregulation and the various adverse effects of the drugs currently available, it is therefore desirable to introduce other norepinephrine/serotonin reuptake inhibitors (NRI/SRI) useful in the treatment of hot flashes.